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Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) for 2,4-Pyridinedicarboxylic acid (CAS no: 499-80-9) was predicted based on OECD QSAR toolbox in rats 2942 mg/kg bw; Danish (Q)SAR Database in rats 5600 mg mg/kg bw and in mice 2900 mg mg/kg bw; and different studies available on structurally similar read across substances Isonicotinic acid (CAS no: 55-22-1) in rats 5000 mg/kg bw and in mice 3123 mg/kg bw; and Phthalic acid (CAS No: 88-99-3) for rats >5000 mg/kg bw. All these studies concluded that the LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 2,4-Pyridinedicarboxylic acid cannot be classified for acute oral toxicity.

Acute Dermal toxicity: 

Acute Dermal toxicity dose (LD50) for 2,4-Pyridinedicarboxylic acid (CAS no: 499-80-9) was predicted based on OECD QSAR toolbox 2633 mg/kg bwand differentstudies available for the structurally similar read across substance 1,4-Benzenedicarboxylic acid (100-21-0) >2000 mg/kg bw and 1,3-Benzenedicarboxylic acid (121-91-5) >2000 mg/kg bw. All these studies concluded that the LD50 value is>2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 2,4-Pyridinedicarboxylic acid cannot be classified for acute dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
Data is predicted using OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached
Qualifier:
according to guideline
Guideline:
other: estimated
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.4
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Specific details on test material used for the study:
Name: 2,4-Pyridinedicarboxylic acid
InChI: 1S/C7H5NO4/c9-6(10)4-1-2-8-5(3-4)7(11)12/h1-3H,(H,9,10)(H,11,12)
Smiles: c1(cc(ncc1)C(O)=O)C(O)=O
- Molecular formula (if other than submission substance):C7H5NO4
- Molecular weight (if other than submission substance):167.12 g/mol
- Substance type:Organic
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
not specified
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
not specified
Doses:
2942 mg/kg
No. of animals per sex per dose:
not specified
Control animals:
not specified
Details on study design:
not specified
Statistics:
not specified
Preliminary study:
not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 942 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality observed
Mortality:
not specified
Clinical signs:
not specified
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and "s" )  and ("t" and ( not "u") )  )  and "v" )  and ("w" and ( not "x") )  )  and ("y" and ( not "z") )  )  and "aa" )  and "ab" )  and ("ac" and ( not "ad") )  )  and ("ae" and ( not "af") )  )  and ("ag" and ( not "ah") )  )  and ("ai" and ( not "aj") )  )  and ("ak" and ( not "al") )  )  and ("am" and "an" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aromatic compound OR Carbonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acid, aromatic attach [-COOH] OR Alcohol, olefinic attach [-OH] OR Aromatic Carbon [C] OR Aromatic Nitrogen OR Carbonyl, olefinic attach [-C(=O)-] OR Carbonyl, one aromatic attach [-C(=O)-] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Pyridine, non fused rings  by Organic functional groups (US EPA) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl OR Carboxylic acid OR Overlapping groups OR Pyridine/ Pyridinium ion by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aryl OR Carboxylic acid OR Pyridine/ Pyridinium ion by Organic Functional groups ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinone methides OR AN2 >>  Michael-type addition, quinoid structures >> Quinones and Trihydroxybenzenes OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> Hydroxamic Acids OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Michael-type conjugate addition to activated alkene derivatives OR AN2 >> Michael-type conjugate addition to activated alkene derivatives >> Alpha-Beta Conjugated Alkene Derivatives with Geminal Electron-Withdrawing Groups OR AN2 >> Nucleophilic addition reaction with cycloisomerization OR AN2 >> Nucleophilic addition reaction with cycloisomerization >> Hydrazine Derivatives OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> Alpha, Beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Alpha, Beta-Unsaturated Aldehydes OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Quinoxaline-Type 1,4-Dioxides OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Thiols OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Acyclic Triazenes OR SN1 >> Nucleophilic attack after carbenium ion formation >> N-Nitroso Compounds OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after nitrosonium cation formation OR SN1 >> Nucleophilic attack after nitrosonium cation formation >> N-Nitroso Compounds OR SN1 >> Nucleophilic substitution on diazonium ion OR SN1 >> Nucleophilic substitution on diazonium ion >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Hydroxamic Acids OR SN2 >> Acylation >> N-Hydroxylamines OR SN2 >> Alkylation OR SN2 >> Alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Direct nucleophilic attack on diazonium cation OR SN2 >> Direct nucleophilic attack on diazonium cation >> Hydrazine Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Schiff base formers OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Alpha-beta-dicarbonyl OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.4

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group >> Arenesulfonamides OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> (Thio)Acyl and (thio)carbamoyl halides and cyanides  OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR Acylation >> Direct acylation involving a leaving group >> N-Carbonyl heteroaryl amines OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR AN2 OR AN2 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha,beta-Unsaturated Carbonyls and Related Compounds OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters >> alpha,beta-Unsaturated Carboxylic Acids and Esters OR AN2 >> Michael-type addition to activated double bonds in vinyl pyridines OR AN2 >> Michael-type addition to activated double bonds in vinyl pyridines >> Ethenyl Pyridines OR AN2 >> Michael-type addition to quinoid structures  OR AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides OR AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines OR AN2 >> Nucleophilic addition at polarized N-functional double bond OR AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulfonamides OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles (hypothesized) >> Heterocyclic Aromatic Amines OR Michael addition OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Conjugated systems with electron withdrawing groups  OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes OR Michael addition >> Michael addition on polarised Alkenes OR Michael addition >> Michael addition on polarised Alkenes >> Polarised Alkene - alkenyl pyridines, pyrazines, pyrimidines or triazines  OR Michael addition >> Michael addition on polarised Alkenes >> Polarised Alkenes - sulfones  OR Michael addition >> Michael addition on polarised Alkynes OR Michael addition >> Michael addition on polarised Alkynes >> Polarised Alkynes - alkinyl pyridines, pyrazines, pyrimidines, triazines  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Radical reactions OR Radical reactions >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base OR Radical reactions >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes OR SE reaction (CYP450-activated heterocyclic amines) OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base  OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base  >> Heterocyclic Aromatic Amines OR SN2 OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Isothiazolone derivatives  OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  OR SR reaction (peroxidase-activated heterocyclic amines) OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines by Protein binding by OASIS v1.4

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OECD

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as No alert found by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Alkyl (C<5) or benzyl ester of sulphonic or phosphonic acid OR alpha,beta-unsaturated carbonyls OR Aromatic mono-and dialkylamine OR Aromatic ring N-oxide OR Hydrazine OR Polycyclic Aromatic Hydrocarbons OR Simple aldehyde by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as No alert found by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Alkali Earth by Groups of elements

Domain logical expression index: "v"

Similarity boundary:Target: OC(=O)c1ccnc(C(O)=O)c1
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Stable form by Tautomers unstable

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Conjugated keto(scy) - 1,5-H shift by Tautomers unstable

Domain logical expression index: "aa"

Similarity boundary:Target: OC(=O)c1ccnc(C(O)=O)c1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "ab"

Similarity boundary:Target: OC(=O)c1ccnc(C(O)=O)c1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg AND Group All Melting Point > 200 C AND Group CN Melting Point > 180 C AND Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as Group CN Aqueous Solubility < 0.1 g/L by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "ae"

Referential boundary: The target chemical should be classified as Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "af"

Referential boundary: The target chemical should be classified as Esters (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "ag"

Referential boundary: The target chemical should be classified as ECHA PR AND EINECS AND REACH ECB AND TSCA by Inventory Affiliation

Domain logical expression index: "ah"

Referential boundary: The target chemical should be classified as (N/A) by Inventory Affiliation

Domain logical expression index: "ai"

Referential boundary: The target chemical should be classified as Acidic [0,10) AND Basic [10,20) by Ionization at pH = 1

Domain logical expression index: "aj"

Referential boundary: The target chemical should be classified as Acidic [40,50) by Ionization at pH = 1

Domain logical expression index: "ak"

Referential boundary: The target chemical should be classified as Acidic [80,90) AND Basic [0,10) by Ionization at pH = 4

Domain logical expression index: "al"

Referential boundary: The target chemical should be classified as Basic [10,20) by Ionization at pH = 4

Domain logical expression index: "am"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.489

Domain logical expression index: "an"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.03

Interpretation of results:
other: Not classified
Conclusions:
LD50 was estimated to be 2942 mg/kg bw, when male and female Wistar rats were treated with 2,4-Pyridinedicarboxylic acid (CAS no: 499-80-9) via oral gavage route.
Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 2,4-Pyridinedicarboxylic acid (CAS no: 499-80-9). The LD50 was estimated to be 2942 mg/kg bw, when male and female Wistar rats were treated with 2,4-Pyridinedicarboxylic acid via oral gavage route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 942 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from QSAR toolbox 3.4.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
Data is predicted using OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached
Qualifier:
according to guideline
Guideline:
other: estimated
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.4
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Specific details on test material used for the study:
Name: 2,4-Pyridinedicarboxylic acid
InChI: 1S/C7H5NO4/c9-6(10)4-1-2-8-5(3-4)7(11)12/h1-3H,(H,9,10)(H,11,12)
Smiles: c1(cc(ncc1)C(O)=O)C(O)=O
- Molecular formula (if other than submission substance):C7H5NO4
- Molecular weight (if other than submission substance):167.12 g/mol
- Substance type:Organic
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
not specified
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
not specified
Duration of exposure:
24 hours
Doses:
2633 mg/kg
No. of animals per sex per dose:
not specified
Control animals:
not specified
Details on study design:
not specified
Statistics:
not specified
Preliminary study:
not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 633 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Mortality:
not specified
Clinical signs:
not specified
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and ("l" and ( not "m") )  )  and "n" )  and ("o" and "p" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aromatic compound OR Carbonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acid, aromatic attach [-COOH] OR Alcohol, olefinic attach [-OH] OR Aromatic Carbon [C] OR Aromatic Nitrogen OR Carbonyl, olefinic attach [-C(=O)-] OR Carbonyl, one aromatic attach [-C(=O)-] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Pyridine, non fused rings  by Organic functional groups (US EPA) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl OR Carboxylic acid OR Overlapping groups OR Pyridine/ Pyridinium ion by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aryl OR Carboxylic acid OR Pyridine/ Pyridinium ion by Organic Functional groups ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinone methides OR AN2 >> Michael-type conjugate addition to activated alkene derivatives OR AN2 >> Michael-type conjugate addition to activated alkene derivatives >> Alpha-Beta Conjugated Alkene Derivatives with Geminal Electron-Withdrawing Groups OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> Alpha, Beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Alpha, Beta-Unsaturated Aldehydes OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR Radical OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Non binder, MW>500 OR Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Halogens OR Metalloids OR Transition Metals by Groups of elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.452

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.87

Interpretation of results:
other: Not classified
Conclusions:
LD50 was estimated to be 2633 mg/kg bw, when New Zealand White male and female rabbit was treated with 2,4-Pyridinedicarboxylic acid (CAS no: 499-80-9) for 24 hours by dermal application occlusively.
Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 2,4-Pyridinedicarboxylic acid (CAS no: 499-80-9). The LD50 was estimated to be 2633 mg/kg bw, when New Zealand White male and female rabbit was treated with 2,4-Pyridinedicarboxylic acid for 24 hours by dermal application occlusively.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 633 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from QSAR toolbox 3.4.

Additional information

Acute oral toxicity:

In different studies, 2,4-Pyridinedicarboxylic acid (CAS no: 499-80-9) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats and mice for 2,4-Pyridinedicarboxylic acid along with the study available on structurally similar read across substances Isonicotinic acid (CAS no: 55-22-1) and Phthalic acid (CAS No: 88-99-3). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 2,4-Pyridinedicarboxylic acid (CAS no: 499-80-9). The LD50 was estimated to be 2942 mg/kg bw, when male and female Wistar rats were treated with 2,4-Pyridinedicarboxylic acid via oral gavage route.

In another study based on the QSAR prediction done using the Danish (Q)SAR Database, the acute oral toxicity was estimated for the 2,4-Pyridinedicarboxylic acid (499-80-9). The LD50 was estimated to be 5600 mg mg/kg bw with Reliability Index 0.7 (0.5-0.75 = moderate prediction quality), when rats were treated with 2,4-Pyridinedicarboxylic acid orally.

The above study is supported by the Danish (Q)SAR Database, for 2,4-Pyridinedicarboxylic acid (499-80-9). The acute oral toxicity dose (LD50) was estimated to be 2900 mg mg/kg bw with Reliability Index 0.76 (>0.75 = high prediction quality), when mice were treated with 2,4-Pyridinedicarboxylic acid orally.

The above studies are supported by Tsarichenko et al. (Pharmaceutical Chemistry Journal, Volume 11, Issue 4, pp 481–483, April 1977), U.S. National Library of Medicine (ChemIDplus, 2017) and IFA GESTIS (GESTIS SUBSTANCE Database, 2017), for the structurally similar read across substance Isonicotinic acid (CAS no: 55-22-1). The acute oral toxicity was tested in rats at the dose concentration of 5000 mg/kg bw. Animals were observed for clinical signs. 50% mortality was observed at 5000 mg/kg with clinical signs such as, suppression of the general motor activity, an impairment of motor coordination of the animal, and its assumption of a lateral position was observed. Therefore, LD50 was considered to be 5000 mg/kg bw, when white rats were treated with Isonicotinic acid via oral gavage route.

This study is also supported by Tsarichenko et al. (Pharmaceutical Chemistry Journal, Volume 11, Issue 4, pp 481–483, April 1977) and U.S. National Library of Medicine (ChemIDplus, 2017), for the structurally similar read across substance Isonicotinic acid (CAS no: 55-22-1). The acute oral toxicity was tested in mice at the dose concentration of 3123 mg/kg bw. Animals were observed for clinical signs. 50% mortality was observed at 3123 mg/kg with clinical signs such as, suppression of the general motor activity, an impairment of motor coordination of the animal, and its assumption of a lateral position was observed. Therefore, LD50 was considered to be 3123 mg/kg with confidential limit of 2504.4-4746.6 mg/kg with s = 2.2, when white mice were treated with Isonicotinic acid via oral gavage route.

All these studies are further supported by Schoneker et al. (Food and Chemical Toxicology 41, 405–413, 2003), for the structurally similar read across substance Phthalic acid (CAS No: 88-99-3). Acute oral toxicity study was conducted in Albino male and female mice at the concentration of 5000 mg/kg bw orally by gavage in 5% gum acacia. No mortality was observed in treated mice at 5000 mg/kg bw.CNS depression and Inflammation of the gastrointestinal tract was observed in treated mice. Therefore, LD50 was considered to >5000 mg/kg bw when Albino male and female mice were treated with Phthalic acid orally by gavage.

Thus, based on the above studies on 2,4-Pyridinedicarboxylic acid (CAS no: 499-80-9) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 2,4-Pyridinedicarboxylic acid cannot be classified for acute oral toxicity.

Acute Dermal toxicity:

In different studies, 2,4-Pyridinedicarboxylic acid (CAS no: 499-80-9) has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rabbits for 2,4-Pyridinedicarboxylic acid along with the study available on the structurally similar read across substance 1,4-Benzenedicarboxylic acid (100-21-0) and 1,3-Benzenedicarboxylic acid (121-91-5). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 2,4-Pyridinedicarboxylic acid (CAS no: 499-80-9). The LD50 was estimated to be 2633 mg/kg bw, when New Zealand White male and female rabbit was treated with 2,4-Pyridinedicarboxylic acid for 24 hours by dermal application occlusively.

This study is supported by U.S. National Library of Medicine (Hazardous Substances Data Bank, 2017), EUROPEAN COMMISSION – European Chemicals Bureau (IUCLID Dataset, 22 - FEB - 2000) and United Nations Environmental Programme (OECD SIDS, 2001), for the structurally similar read across substance 1,4-Benzenedicarboxylic acid (100-21-0). Acute dermal toxicity study was conducted in 10 Male and female New Zealand rabbits at the concentration of 2000mg/kg bw. The test material (Terephthalic acid was supplied by the Amoco Corporation; Purity exceeds 99%) was applied on the back and covered with an occlusive wrap. Prior to application, the backs were shaved and moistened with water. Animals were observed daily for Mortality and general symptoms; Body weights were assessed at dosing, and on Days 7 and 14.No mortality observed at 2000 mg/kg bw. Clinical signs noted consisted of an erythema at the application site immediately after unwrapping in 2/5 males and 4/5 females. All animals appeared normal by Day 4. Mean body weights increased during the study. No alterations were noted during gross necropsy. Therefore, LD50 was considered to be >2000 mg/kg bw, when Male and female New Zealand rabbits were treated with 1,4-Benzenedicarboxylic acid occlusively to the skin.

The above study is further supported by IFA GESTIS (GESTIS SUBSTANCE Database, 2017) and United Nations Environmental Programme (OECD SIDS, 2002), for the functionally similar read across substance 1,3-Benzenedicarboxylic acid (121-91-5). Acute dermal toxicity study was conducted in 10 Male and female New Zealand White rabbits at the concentration of 2000 mg/kg bw. The test material was applied to the clipped back of each animal for 24 hours. Animals were observed daily for Mortality, clinical signs and body weight change. No mortality observed at 2000 mg/kg bw. Mild dermal irritation was observed in 4 animals immediately following unwrapping. No adverse treatment-related clinical signs were observed. Mean body weights increased during the study. No gross pathological lesions due to treatment were evident in any of the animals at necropsy. Therefore, LD50 was considered to be >2000 mg/kg bw, when Male and female New Zealand White rabbits were treated with 1,3-Benzenedicarboxylic acid occlusively to the clipped back skin.

Thus, based on the above studies on 2,4-Pyridinedicarboxylic acid (CAS no: 499-80-9) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 2,4-Pyridinedicarboxylic acid cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on 2,4-Pyridinedicarboxylic acid (CAS no: 499-80-9) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw for acute oral and dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, 2,4-Pyridinedicarboxylic acid cannot be classified for acute oral and dermal toxicity.